Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol?
In the present study acute effects of ethanol on [3H]-acetylcholine ([3H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [3H]-ACh release (Ig EC50 = -4.10, CI95 = [-4.14, -4.05]) was inhibited by strychnine in a competitive manner (pA2 = 6.86, CI95 = [6.61, 7.08]). Release of [3H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (Ig EC50 = -2.61, CI95 = [-2.69, -2.52]). Both glycine and L-serine showed similar maximum effects (Emax(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) = 1.19, CI95 = [1.09, 1.32]). Ethanol at concentrations of 2%/1000 (= 34 mM) and 4%/1000 (= 68 mM) inhibited glycine-evoked [3H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA2 of ethanol was 1.19, CI95 = [0.85, 1.41], at 2%/1000 [v/v] and 1.51, CI95 = [1.19, 1.78] at 4%/1000 ethanol. Similar to its action on glycine-evoked [3H]-ACh release, ethanol at 4%/1000 [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA2 = 0.83, CI95 = [-0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [3H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.
Darstein
M
M
Sektion Klinische Neuropharmakologie der Neurologischen Universitätsklinik, Neurozentrum, Freiburg, Germany.
Löschmann
P A
PA
Knörle
R
R
Feuerstein
T J
TJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018118:Chloride Channels / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D008297:Male; D011699:Putamen / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology; D012694:Serine / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018118:Chloride Channels; D018009:Receptors, Glycine; D000431:Ethanol; D018698:Glutamic Acid; D012694:Serine; D000109:Acetylcholine; D005998:Glycine